Addiction to nicotine is highly prevalent in the adolescent population, yet little research has examined the neurobiology of nicotine in adolescence. The brain continues to undergo developmental changes in adolescence. These changes are particularly evident in the prefrontal cortex, a region critical for risk assessment and impulse control. The changes produced by nicotine in adult rat models are well documented, and it is well known that nicotine exposure during early development causes neurobehavioral defects. However, the effects of nicotine on rat adolescent behavior and development are not well documented. Not only may nicotine exposure during this critical period of development have different effects on the brain, but may cause long-lasting alterations in the prefrontal cortex. The proposed research will investigate the sensitivity of adolescent rats to nicotine, the development of drug-associated cue conditioning to nicotine, and the gene-expression changes in adolescent prefrontal cortex. In addition, the long-term effects of nicotine exposure in adolescence on drug sensitivity will be examined. The underlying notion is that the substrate of the adolescent brain is fundamentally different than that of the adult brain, and the effects of nicotine addiction may be more lasting and profound than is currently known, particularly in regions involved in executive control of behavior, such as the prefrontal cortex.